Navigation Links
Diverse genetic abnormalities lead to NF-κB activation in multiple myeloma

Two new studies may lead to the development of more effective therapies for individuals with multiple myeloma (MM), a common and incurable blood cell cancer. The research, published by Cell Press in the August issue of the journal Cancer Cell, provides new insight into the molecular mechanisms that underlie aberrant NF-κB activity in MM tumor cells and underscores the relevance of the NF-κB signaling pathway as a target for MM therapy.

MM is a cancer of the plasma cell, a blood cell that produces antibodies to help the body fight off infections. Previous research implicates abnormal activation of the NF-κB signaling pathway as a key event in MM pathology. NF-κB target genes are known to be involved in cell proliferation and cell survival. Although there is significant overlap and interplay between them, there are two separate pathways that lead to activation of NF-κB, the classical pathway and the alternative pathway.

Constitutive activation of NF-κB to block apoptosis has been implicated in various types of cancer, but the molecular mechanisms involved are not well understood. Two separate research groups used a variety of sophisticated genomic techniques to examine mutations in hundreds of MM patient samples and cell lines to identify mutations that impact NF-κB activation.

Dr. Louis M. Staudt from the National Cancer Institute led a research group who revealed the importance of both the classical and alternative NF-κB pathways in MM pathogenesis. Most MM patient samples examined exhibited NF-κB pathway activation via diverse genetic abnormalities. Importantly, targeted disruption of the classical NF-κB signaling blocked myeloma proliferation and induced cell death. These genetic and functional data provide a molecular framework for the rational development of NF-κB pathway inhibitors for the therapy of MM, offers Dr. Staudt.

In a separate study, Dr. Rafael Fonseca, from the Mayo Clinic Arizona, and colleagues report mutations in several genes that result in constitutive activation of the alternative NF-κB pathway. We propose that the acquisition of the mutations identified in our study results in the accumulation of malignant plasma cells beyond the physiological control of the bone marrow compartment. Our results suggest a mechanism by which MM cells can overcome these limitations through acquisition of mutations that result in constitutive and ligand-independent activation of the alternative NF-κB pathway, explains Dr. Fonseca.

Taken together, results for these studies define diverse mutations that lead to pathological activation of NF-κB signaling in MM and describe a shift of plasma cells from dependence on the microenvironment to an environment-independent state during progression of MM. Regardless of the specific method of activation, the NF-κB pathway plays a central role in MM pathogenesis and is an excellent target for development of new therapeutics.

Contact: Erin Doonan
Cell Press

Related biology news :

1. Diverse tropical forests defy metabolic ecology models
2. Novel Asthma Study Shows Multiple Genetic Input Required; Single-gene Solution Shot Down
3. Its not all genetic: Common epigenetic problem doubles cancer risk in mice
4. Scientists detect probable genetic cause of some Parkinsons disease cases
5. Mouse brain tumors mimic those in human genetic disorder
6. Genetically modified natural killer immune cells attack, kill leukemia cells
7. Scientists identify genetic pathways essential to RNA interference
8. Ants Genetic Engineering Leads To Species Interdependency
9. Researchers trace evolution to relatively simple genetic changes
10. Genetic Variation Visualization - From EMBL
11. Genetically modified rice in China benefits farmers health, study finds
Post Your Comments:
(Date:10/29/2015)... , Oct. 29, 2015  Rubicon Genomics, Inc., ... U.S. distribution of its DNA library preparation products, ... Rubicon,s new ThruPLEX Plasma-seq kit. ThruPLEX Plasma-seq has ... preparation of NGS libraries for liquid biopsies--the analysis ... and prognostic applications in cancer and other conditions. ...
(Date:10/27/2015)... -- In the present market scenario, security is one ... verticals such as banking, healthcare, defense, electronic gadgets, and ... secure & simplified access control and growing rate of ... bank accounts, misuse of users, , and so on. ... and smartphones are expected to provide potential opportunities for ...
(Date:10/26/2015)... and LAS VEGAS , Oct. ... Labs , an innovator in modern authentication and a ... announced the launch of its latest version of the ... enabling organizations to use standards-based authentication that supports existing ... S3 Authentication Suite is ideal for organizations deploying customer-facing ...
Breaking Biology News(10 mins):
(Date:11/27/2015)... PA (PRWEB) , ... November 27, 2015 , ... ... Technical Program that includes over 2,000 technical presentations offered in symposia, oral ... chemistry and applied spectroscopy, covers a wide range of applications such as, but ...
(Date:11/26/2015)... MUMBAI , November 26, 2015 ... --> Accutest Research ... accredited Contract Research Organization (CRO), has ... Chase Cancer Center - Temple Health ... ,     (Photo: ) ...
(Date:11/25/2015)... , November 26, 2015 ... Global Biobanking Market 2016 - 2020 report analyzes ... maintaining integrity and quality in long-term samples, minimizing ... long-term cost-effectiveness. Automation minimizes manual errors such as ... technical efficiency. Further, it plays a vital role ...
(Date:11/25/2015)... -- 2 nouvelles études permettent d , ... entre les souches bactériennes retrouvées dans la plaque ... . Ces recherches  ouvrent une nouvelle voie ... efficace de l,un des problèmes de santé les ...    --> 2 nouvelles études permettent d ...
Breaking Biology Technology: